Plasma catecholamine levels in the early stages of treatment-naïve Parkinson’s disease

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Abstract

Rationale: Parkinson's disease (PD) is a neurodegenerative disorder with predominant involvement of catecholamine-producing neurons of the central and peripheral nervous system. Taking into account the relative availability and low costs of plasma catecholamine measurements, it is worthwhile to study these parameters as biomarkers of the early stages of PD.

Aim: To determinate whether plasma levels of dopamine (DA), norepinephrine (NE), L-3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) in patients with early stages of PD are related with akinetic-rigid and tremor-dominant variants and to compare the results to healthy volunteers.

Materials and methods: This was an observational cross-sectional cohort study performed from 2012 to 2015. The main study group included unselected outpatients who attended the Republican Consultative and Diagnostic Center of Movement Disorders and Botulinotherapy (Kazan, Russia) with newly diagnosed early PD (Hoehn and Yahr stages I and II, 1967), of various ages and both genders, who had not been given any specific antiparkinsonian treatment. The control group included healthy volunteers with no clinical signs of PD (they could have other chronic diseases of the non-extrapyramidal origin). Plasma catecholamine levels were measured by gas liquid chromatography.

Results: One hundred and thirty (130) treatment-naïve patients with newly diagnosed PD (mean age 59.34 ± 8.42 years, male gender 45.38%) were enrolled into the main study group. The control group included 56 healthy volunteers matched for age and gender. The distribution of various PD forms and stages was as follows: PD tremor-dominant variant 56.9%, PD akinetic-rigid variant 43.1%; PD stage I 76.9%, PD stage II 23.1%. Irrespective of the variant and stage, the PD patients demonstrated decreased NE levels, compared to the controls (95% confidence intervals 124–216 and 248–428 pg/mL, respectively, р < 0.026). DOPA plasma level was reduced only in the patients with akinetic-rigid PD variant (р = 0.017), while DOPAC level in the patients with PD stage II (р = 0.008). The average DA:NE:DOPA:DOPAC ratio was 1:32:105:64 in the control group, 1:62:238:88 in the patients with PD tremor-dominant variant (the difference is significant for NE and DOPA, р < 0.05), and 1:29:96:32 in those with PD akinetic-rigid variant (p > 0.05). In the healthy controls the changes in DOPA levels account for 84% of the DA and NE variability; no correlation between DOPAC and other catecholamines was found. On the contrary, in the PD patients regardless of the stage and the disease variant, DOPAC levels directly correlated with DA (p < 0.04). The PD tremor-dominant variant patients demonstrated a direct correlation between plasma NE and DOPA levels (p < 0.05).

Conclusion: The results obtained on absolute and relative parameters catecholamine turnover in the patients with early PD stages support the hypothesis on different pathophysiology of the tremor-dominant and akinetic-rigid variants of PD.

About the authors

Z. A. Zalyalova

Kazan State Medical University;
Republican Consultative and Diagnostic Center of Movement Disorders and Botulinotherapy

Author for correspondence.
Email: z.zalyalova@gmail.com

Zuleykha A. Zalyalova – MD, PhD, Professor, Neurology and Rehabilitation Department Kazan State Medical University, Head Republican Consultative and Diagnostic Center of Movement Disorders and Botulinotherapy

49 Butlerova ul., Kazan, 420012,

 5 Isaeva ul., Kazan, 420029

Russian Federation

D. M. Khasanova

Republican Consultative and Diagnostic Center of Movement Disorders and Botulinotherapy

Email: fake@neicon.ru

Diana M. Khasanova – MD, PhD, Neurologist 

 5 Isaeva ul., Kazan, 420029

Russian Federation

M. V. Ugrumov

Koltzov Institute of Dеvеlорmеntаl Biology of Russiаn Асаdеmу of Sciences

Email: fake@neicon.ru

Michael V. Ugrumov – Member of Russian Academy of Sciences, ScD in Biology, Head of Laboratory of Neural and Neuroendocrine Regulations

26 Vavilova ul., Moscow,119334

Russian Federation

References

  1. Goldman JG, Postuma R. Premotor and nonmotor features of Parkinson's disease. Curr Opin Neurol. 2014;27(4):434–41. doi: 10.1097/WCO.0000000000000112.
  2. Залялова ЗА, Хасанова ДМ. Депрессия у пациентов с ранними стадиями болезни Паркинсона. Трудный пациент. 2016;(4–5): 22–8.
  3. Goldstein DS, Holmes C, Sharabi Y. Cerebrospinal fluid biomarkers of central catecholamine defciency in Parkinson's disease and other synucleinopathies. Brain. 2012;135(Pt 6):1900– 13. doi: 10.1093/brain/aws055.
  4. Delaville C, Deurwaerdère PD, Benazzouz A. Noradrenaline and Parkinson's disease. Front Syst Neurosci. 2011;5:31. doi: 10.3389/fnsys.2011.00031.
  5. Угрюмов МВ, ред. Нейродегенеративные заболевания: от генома до целостного организма. Т. 1. М.: Научный мир; 2014; 580 с.
  6. Biomarkers Defnitions Working Group. Biomarkers and surrogate endpoints: preferred defnitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. doi: 10.1067/mcp.2001.113989.
  7. Eldrup E, Mogensen P, Jacobsen J, Pakkenberg H, Christensen NJ. CSF and plasma concentrations of free norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenylalanine (DOPA), and epnephrine in Parkinson's disease. Acta Neurol Scand. 1995;92(2):116–21. doi: 10.1111/j.16000404.1995.tb01023.x.
  8. Lewitt PA. Norepinephrine: the next therapeutics frontier for Parkinson's disease. Transl Neurodegener. 2012;1(1):4. doi: 10.1186/20479158-1-4.
  9. Веселова ИА, Сергеева ЕА, Македонская МИ, Еремина ОЕ, Калмыков СН, Шеховцова ТН. Методы определения маркеров нейромедиаторного обмена в целях клинической диагностики. Журнал аналитической химии. 2016;71(12):1235–49. doi: 10.7868/S0044450216120124.
  10. Goldstein DS, Holmes C. Neuronal source of plasma dopamine. Clin Chem. 2008;54(11): 1864–71. doi: 10.1373/clinchem.2008.107193.
  11. Pearse AG. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. 1969;17(5): 303–13. doi: 10.1177/17.5.303.
  12. Wahbe F, Hagege J, Loreau N, Ardaillou R. Endogenous dopamine synthesis and dopa-decarboxylase activity in rat renal cortex. Mol Cell Endocrinol. 1982;27(1):45–54. doi: 10.1016/0303-7207(82)90061-2.
  13. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197–211. doi: 10.1016/S0197-4580(02)00065-9.
  14. Braak H, Del Tredici K. Invited Article: Nervous system pathology in sporadic Parkinson disease. Neurology. 2008;70(20):1916–25. doi: 10.1212/01.wnl.0000312279.49272.9f.
  15. Селихова МВ, Коган БВ, Серкин ГВ, Гусев ЕИ. Обмен катехоламинов при разных формах болезни Паркинсона. Журнал неврологии и психиатрии им. С.С. Корсакова. 2002;102(9):37–40.
  16. Marras C, Chaudhuri KR. Nonmotor features of Parkinson's disease subtypes. Mov Disord. 2016;31(8):1095–102. doi: 10.1002/mds.26510.
  17. Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ. A clinico-pathological study of subtypes in Parkinson's disease. Brain. 2009;132(Pt 11):2947–57. doi: 10.1093/brain/awp234.
  18. Thenganatt MA, Jankovic J. Parkinson disease subtypes. JAMA Neurol. 2014;71(4):499–504. doi: 10.1001/jamaneurol.2013.6233.
  19. Siderowf A, Newberg A, Chou KL, Lloyd M, Colcher A, Hurtig HI, Stern MB, Doty RL, Mozley PD, Wintering N, Duda JE, Weintraub D, Moberg PJ. [99mTc]TRODAT-1 SPECT imaging correlates with odor identifcation in early Parkinson disease. Neurology. 2005;64(10):1716–20. doi: 10.1212/01.WNL.0000161874.52302.5D.
  20. Niethammer M, Feigin A, Eidelberg D. Functional neuroimaging in Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2(5):a009274. doi: 10.1101/cshperspect.a009274.
  21. Залялова ЗА. Дрожательные фенотипы болезни Паркинсона. В: Иллариошкин СН, Левин ОС, ред. Болезнь Паркинсона и расстройства движений. Руководство для врачей по материалам II Национального конгресса по болезни Паркинсона и расстройствам движений (с международным участием). М.: Серебряные нити; 2011. с. 55–9

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Copyright (c) 2018 Zalyalova Z.A., Khasanova D.M., Ugrumov M.V.

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